The effects of administration of monoamine oxidase-B inhibitors on rat striatal neurone responses to dopamine

Br J Pharmacol. 1994 Dec;113(4):1159-66. doi: 10.1111/j.1476-5381.1994.tb17119.x.


1. (-)-Deprenyl has been shown to potentiate rat striatal neurone responses to dopamine agonists at doses not altering dopamine metabolism. Since there are a number of effects of (-)-deprenyl which could result in this phenomenon, we have investigated the effects of MDL 72,145 and Ro 19-6327, whose only common effect with (-)-deprenyl is an inhibition of monoamine oxidase-B (MAO-B), on rat striatal neurone responses to dopamine and on striatal dopamine metabolism. 2. Using in vivo electrophysiology, i.p. injection of either MDL 72,145 or Ro 19-6327 was found to produce a dose-dependent potentiation of striatal neurone responses to dopamine but not gamma-aminobutyric acid. 3. Neurochemical investigations revealed that this occurred at doses (0.25-1 mg kg-1) which, while not affecting levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid or homovanillic acid, did cause a significant, dose-dependent, elevation in striatal levels of the putative neuromodulator, 2-phenylethylamine (PE). 4. Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327. 5. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg-1) selective for reduction of elevated PE levels. 6. These results suggest that PE can act as a neuromodulator of dopaminergic responses and that MAO-B inhibitors may potentiate neuronal responses to dopamine via the indirect mechanism of elevation of PE following MAO-B inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Allylamine / analogs & derivatives
  • Allylamine / pharmacology
  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Electrophysiology
  • Homovanillic Acid / metabolism
  • Hydrazines / pharmacology
  • Male
  • Microelectrodes
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Phenylephrine / metabolism
  • Phenylephrine / pharmacology
  • Picolinic Acids / pharmacology
  • Rats
  • Rats, Wistar
  • gamma-Aminobutyric Acid / pharmacology


  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Hydrazines
  • Monoamine Oxidase Inhibitors
  • Picolinic Acids
  • 3,4-Dihydroxyphenylacetic Acid
  • Phenylephrine
  • lazabemide
  • Allylamine
  • gamma-Aminobutyric Acid
  • 2-(3,4-dimethoxyphenyl)-3-fluoroallylamine
  • 3-hydroxybenzylhydrazine
  • Dopamine
  • Homovanillic Acid